2,5-Dibromobenzotrifluoride - ≥98% , CAS No.7657-09-2

CAS: 7657-09-2 Cat. No.: D123763 分子式: C₇H₃Br₂F₃ 分子量: 303.9 Beilstein Registry Number: 2261093 EC番号: 231-620-1

グレード＆純度 ≥98%

Synonyms

MFCD00013554 | EINECS 231-620-1 | 1,4-dibromo-2-trifluoromethylbenzene | 1,4-dibromo-2-trifluoromethyl-benzene | 2,5-Dibromobenzotrifluoride, 98% | NCIOpen2_009660 | PS-7117 | 2,5-dibromobenzenetrifluoride | 1,4-dibro-mo-2-(trifluoromethyl)benzene | 1,4-D

Storage

Room temperature

Shipped In

Normal

概要

Product Description

2,5-Dibromobenzotrifluoride is a halogenated hydrocarbon.

Product Application

2,5-Dibromobenzotrifluoride (1,4-Dibromo-2-(trifluoromethyl)benzene) may be used to synthesize 4-bromo-2-(trifluoromethyl)benzaldehyde and functionalized alkynyl-substituted (trifluoromethyl)benzenes.

仕様

同義語

MFCD00013554 | EINECS 231-620-1 | 1,4-dibromo-2-trifluoromethylbenzene | 1,4-dibromo-2-trifluoromethyl-benzene | 2,5-Dibromobenzotrifluoride, 98% | NCIOpen2_009660 | PS-7117 | 2,5-dibromobenzenetrifluoride | 1,4-dibro-mo-2-(trifluoromethyl)benzene | 1,4-D

仕様と純度

≥98%

保管条件

Room temperature

入荷

Normal

純度

≥98%

名前と識別子

パブケム・シド

488186050

パブケム・シド・ウル

https://pubchem.ncbi.nlm.nih.gov/substance/488186050

カノニカル・スマイル

C1=CC(=C(C=C1Br)C(F)(F)F)Br

IUPAC Name

1,4-dibromo-2-(trifluoromethyl)benzene

InChIKey

VWKFJAOCLPPQGR-UHFFFAOYSA-N

INCHI

1S/C7H3Br2F3/c8-4-1-2-6(9)5(3-4)7(10,11)12/h1-3H

異性体SMILES

C1=CC(=C(C=C1Br)C(F)(F)F)Br

WGKドイツ

3

分子量

303.9

Beilstein

2261093

Reaxy-Rn

2261093

Reaxys-RN_link_address

https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=2261093&ln=

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Benzenoids
    • 分類 Benzene and substituted derivatives
      • Subclass Trifluoromethylbenzenes

• Kingdom: Organic compounds
• Superclass: Benzenoids
• 分類: Benzene and substituted derivatives
• Subclass: Trifluoromethylbenzenes
• Intermediate Tree Nodes: Not available
• Direct Parent: Trifluoromethylbenzenes
• Alternative Parents: Bromobenzenes Aryl bromides Organofluorides Organobromides Hydrocarbon derivatives Alkyl fluorides
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: Trifluoromethylbenzene - Halobenzene - Bromobenzene - Aryl halide - Aryl bromide - Hydrocarbon derivative - Organofluoride - Organobromide - Organohalogen compound - Alkyl halide - Alkyl fluoride - Aromatic homomonocyclic compound
• 説明: This compound belongs to the class of organic compounds known as trifluoromethylbenzenes. These are organofluorine compounds that contain a benzene ring substituted with one or more trifluoromethyl groups.
• External Descriptors: Not available

Data sources

1. Djoumbou Feunang Y, Eisner R, Knox C, Chepelev L, Hastings J, Owen G, Fahy E, Steinbeck C, Subramanian S, Bolton E, Greiner R, and Wishart DS. ClassyFire: Automated Chemical Classification With A Comprehensive, Computable Taxonomy. Journal of Cheminformatics, 2016, 8:61.

DOI: 10.1186/s13321-016-0174-y

化学的性質と物理的性質

• 溶解度: Soluble in methanol
• 屈折率: 1.52
• 引火点（°F）: >100°C
• 引火点（°C）: >100°C
• 沸点（°C）: 210°C
• 融点（°C）: 47-51°C
• 分子量: 303.900 g/mol
• XLogP3: 4.200
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 0
• Exact Mass: 303.853 Da
• Monoisotopic Mass: 301.855 Da
• Topological Polar Surface Area: 0.000 Ų
• Heavy Atom Count: 12
• Formal Charge: 0
• Complexity: 157.000
• Isotope Atom Count: 0
• Defined Atom Stereocenter Count: 0
• Undefined Atom Stereocenter Count: 0
• Defined Bond Stereocenter Count: 0
• Undefined Bond Stereocenter Count: 0
• The total count of all stereochemical bonds: 0
• Covalently-Bonded Unit Count: 1

Application Protocols

No assay or immunoapplication protocols are provided for this small-molecule reagent.

Practical laboratory usage (general guidance):

• For cross-coupling, see Reaction Conditions for starting points and adjust ligand/base/solvent based on coupling partner.
• For analytical verification, prepare solutions in CDCl3, DMSO-d6, or acetone-d6 for NMR; typical 19F NMR shows a singlet for CF3 (literature). Use GC–MS or LC–MS for reaction monitoring.

Biological Roles

This compound is a synthetic aromatic building block and does not have established endogenous biological roles.

General notes (literature/chemical biology perspective):

• The trifluoromethyl (CF3) group is a pharmacophore motif frequently used to modulate lipophilicity, metabolic stability, and binding interactions of drug-like molecules. Incorporation via cross-coupling of CF3-bearing aryl halides like this substrate is common in medicinal chemistry campaigns.
• Halogenated aromatics can engage in halogen bonding with protein residues (e.g., C=O of backbone, side-chain heteroatoms), but such interactions depend on the final product structure and context, not on this intermediate per se.
• No known biochemical pathway utilizes 2,5-dibromobenzotrifluoride directly; any bioactivity pertains to derivatives synthesized from it.

Regulatory/usage context:

• For research use only (as stated in Product Data). Not for human or veterinary use, diagnostic procedures, or clinical applications.

If biological testing is planned for products derived from this intermediate, ensure removal of residual palladium/nickel and aryl bromide starting material below relevant thresholds (analytical verification by ICP-MS/ICP-OES, GC/LC).

Buffer Applications

Not typically applicable. 2,5-Dibromobenzotrifluoride is a hydrophobic organic building block, not used as an aqueous buffer component.

Practical guidance:

• If handling in aqueous systems (e.g., phase-transfer reactions), choose compatible organic/aqueous biphasic conditions and appropriate bases (K2CO3, NaOH) with a phase-transfer catalyst. For analytical sample prep, dissolve in an organic solvent (e.g., acetonitrile, DMSO) before dilution if needed.

Green Alternatives

While 2,5-dibromobenzotrifluoride itself is the desired building block, greener choices often concern the reaction media and catalysts used with it.

Strategies (literature-based):

• Solvent substitution: • Replace DMF/DMAc/NMP with 2-MeTHF, CPME, or anisole/toluene where feasible (often effective for Suzuki and Buchwald–Hartwig couplings).
  • Use aqueous micellar media (e.g., TPGS-750-M) for Suzuki couplings to reduce organic solvent load; pair with K2CO3/K3PO4 bases.
  • Consider bio-derived alcohols (ethanol, isopropanol) as co-solvents in Suzuki reactions with water.
• Catalysis efficiency: • Employ highly active Pd catalysts (e.g., Buchwald precatalysts) at ppm–0.1 mol% loadings to minimize precious metal usage.
  • Nickel catalysis can work for aryl bromides, potentially at lower cost and with less environmental impact; ligand selection is critical.
• Base and workup: • Inorganic carbonate/phosphate bases avoid strong caustics; aqueous workups with phase separation reduce solvent consumption.
  • Solid-supported scavengers can curtail metal residues, simplifying purification.
• Energy: • Microwave or flow chemistry can cut reaction times and energy use; flow also improves heat/mass transfer for high-boiling substrates.

Compact comparison (literature guidance):

• Traditional: DMF, 100–140 °C, 1–3 mol% Pd.
• Greener: 2-MeTHF or water/EtOH, 60–100 °C, 0.05–0.5 mol% Pd (or Ni), micellar catalysis where compatible.

Trade-offs: Greener solvents may reduce substrate solubility; modest temperature increases, surfactants, or cosolvent blends often mitigate this.

Pharmaceutical Uses

No direct excipient or pharmacopoeial role is established for 2,5-dibromobenzotrifluoride.

Context for process/formulation chemists (literature/general):

• This material serves as a synthetic intermediate for CF3-containing biaryl/arylamine motifs often explored in medicinal chemistry. It may appear in early-route steps for active pharmaceutical ingredient (API) synthesis, but it is not itself a formulated component.
• Handling in GMP environments typically focuses on:
  • Control of residual palladium/nickel after coupling transformations (use scavengers, activated carbon).
  • Control of aryl bromide carryover in downstream steps (validated purge via crystallization or chromatography).
  • Documentation of impurity profiles (regioisomeric/overbrominated species) and stability under storage.
• If used in process development, select greener solvents where possible and define hold times to prevent protodehalogenation or hydrodebromination under basic aqueous workups.

Note: No medical or therapeutic claims are made for this product. It is offered strictly for research and laboratory synthesis.

Physical Properties

Item-specific specifications are not provided in the Product Data.

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular weight: Not specified for this item; refer to CoA/Spec Sheet.
  • Typical MW (literature for C7H3Br2F3): ~303.90 g/mol
• Molecular formula: Not specified for this item; refer to CoA/Spec Sheet.
  • Typical formula (literature): C7H3Br2F3
• Boiling point: Not specified for this item; refer to CoA/Spec Sheet.
  • Aryl bromides bearing CF3 commonly boil in the ~200–250 °C range (literature, compound-specific values vary).
• Melting point: Not specified for this item; refer to CoA/Spec Sheet.
  • Isomeric dibromobenzotrifluorides may be low-melting solids or high-boiling liquids (literature, varies by isomer and purity).
• Density: Not specified for this item; refer to CoA/Spec Sheet.
  • Halogenated aromatics with Br/CF3 typically exhibit densities >1.5 g/mL (literature trend; compound-specific value required for calculations).
• Refractive index: Not specified for this item; refer to CoA/Spec Sheet.
• Vapor pressure: Not specified for this item; refer to CoA/Spec Sheet.
• Solubility: Not specified for this item; refer to CoA/Spec Sheet.
  • Qualitative (literature): sparingly soluble in water; soluble in nonpolar and moderately polar organic solvents (e.g., toluene, THF, DMF, DCM, acetone).
• LogP: Not specified for this item; refer to CoA/Spec Sheet.
  • Expect high hydrophobicity due to two bromides + CF3 (literature expectation).

Note: For precise physical constants and any assay-limiting impurities (e.g., water, metals), consult the specific lot CoA/SDS.

Quality and Grades

• Grade/purity: Not specified for this item; refer to CoA/Spec Sheet.

Context for this product type (general guidance):

• For cross-coupling applications, trace metal content, halide purity, and low protic impurities (water, alcohols) can impact reactivity and catalyst lifetime. If HPLC/GC assay, water content (Karl Fischer), and residual solvent data are required, request the lot-specific CoA.
• Halogenated aromatic building blocks are often offered as “95%+” or “98%+” assays (GC/HPLC). Higher assay grades reduce byproducts from homocoupling or protodehalogenation and can improve reproducibility in medicinal chemistry.
• Stabilizers: Typically none are added to aryl bromides; if a stabilizer or inhibitor is present, it will be declared on the CoA/label. For moisture control, storage in tightly sealed containers is sufficient under ambient conditions unless otherwise noted.
• UV-Vis background: If using in photoredox reactions or analytical detection near 254 nm, note that aromatic halides absorb in the UV; request a UV cutoff only if critical (Not specified for this item; refer to CoA/Spec Sheet).

Verification tips:

• Check identity via 1H/13C/19F NMR (diagnostic CF3 19F at approximately −63 to −66 ppm; literature), HRMS (M, M+2, M+4 isotopic pattern for Br2), and GC–MS retention.
• Confirm isomer identity (2,5-substitution) by coupling patterns and NOE/2D NMR (literature approach).

Reaction and Applications

Applications (literature/general for aryl bromides with CF3):

• Cross-coupling platform: The two aryl–Br bonds enable diverse Pd/Ni-catalyzed couplings.
  • Suzuki–Miyaura arylation to introduce (hetero)aryl groups at C2 and/or C5.
  • Buchwald–Hartwig amination for diarylamines/anilides.
  • Sonogashira coupling with terminal alkynes; follow-up cyclizations possible.
  • Kumada (with Grignards) and Negishi (with organozincs) under mild conditions.
• Sequential/orthogonal coupling: Electronic effects from the CF3 group can bias oxidative addition rates at the two C–Br sites, enabling regioselective stepwise functionalization (literature: rate differences between positions can be catalyst/ligand controlled).
• Electrophilic aromatic substitution: Deactivated by CF3; nitration/sulfonation are disfavored, improving chemoselectivity for cross-coupling vs EAS.
• Directed metalation/minor pathways: CF3 is not a classic directing group; however, halogen–lithium exchange at very low temperature (e.g., with n-BuLi/i-PrMgCl·LiCl) can provide lithiated intermediates for formylation/carboxylation, but caution is required due to potential decomposition and competitive lithium–halogen exchange (literature).
• Synthesis context: The 2,5-disubstitution pattern is valuable for preparing CF3-containing para- and meta-relationships across the ring, common in agrochemical and medicinal chemistry SAR libraries.

Practical notes:

• Use rigorously anhydrous, degassed conditions for Pd-catalyzed couplings.
• Bulky electron-rich phosphines or NHC ligands accelerate oxidative addition to aryl bromides; bases such as K3PO4, Cs2CO3, or NaOtBu are common.
• Monitor for protodebromination at high temperature; lowering temperature or changing ligand/base often mitigates this side reaction.

Reaction Conditions

The following are general, literature-based conditions for aryl bromides bearing CF3 groups; they are not item-specific specifications.

Suzuki–Miyaura coupling (aryl/heteroaryl boron partners):

• Catalyst: 0.5–2 mol% Pd(PPh3)4 or Pd-PEPPSI/Pd-precatalysts (e.g., XPhos G3).
• Base: K3PO4 (2–3 equiv) or Cs2CO3; aqueous K2CO3 viable for less hindered systems.
• Solvent: toluene/dioxane/H2O (2:1:1) or 2-MeTHF/H2O.
• Temperature/time: 60–100 °C, 2–16 h.
• Notes: Electron-withdrawing CF3 can slow oxidative addition; more electron-rich ligands (XPhos, SPhos, tBuXPhos) often improve rates.

Buchwald–Hartwig amination (amines/anilines):

• Catalyst/ligand: Pd2(dba)3 (1–2 mol% Pd) with BINAP, XPhos, or BrettPhos; or precatalysts.
• Base: NaOtBu, Cs2CO3, or K3PO4 (2–3 equiv).
• Solvent: toluene or dioxane; sometimes DME/THF.
• Temperature/time: 80–110 °C, 4–18 h.
• Notes: Secondary amines generally couple faster than anilines; add molecular sieves to limit hydrodehalogenation.

Sonogashira coupling (terminal alkynes):

• Catalyst: Pd(PPh3)2Cl2 (1 mol% Pd) + CuI (2–5 mol%).
• Base: Et3N or DIPEA (2–3 equiv).
• Solvent: THF, DMF, or toluene.
• Temperature/time: rt–80 °C, 2–12 h.
• Notes: For copper-free variants, use Pd/NHC catalysts to minimize Glaser homocoupling.

Negishi/Kumada (organozinc/Grignard):

• Catalyst: Pd(PPh3)4 or NiCl2(dppp).
• Solvent: THF/ether.
• Temperature: 0–50 °C.
• Notes: Control equivalents to avoid double substitution if mono-functionalization is intended.

Workup: Quench with water, extract with organic solvent, filter through silica or metal scavengers, and purify by column chromatography or crystallization. Analyze by 1H/13C/19F NMR and GC/LC–MS.

Safety and Handling

• GHS classification: Not specified for this item; refer to SDS for authoritative classification and pictograms.
• Signal word / H-statements: Not specified for this item; refer to SDS.

General safety guidance for halogenated aromatics (literature/industry practice):

• Hazards: May cause skin and eye irritation; harmful if swallowed or inhaled; potential aquatic toxicity. Avoid aerosols and vapor inhalation during heating.
• PPE: Use chemical-resistant gloves (e.g., nitrile), lab coat, and splash goggles. Handle in a fume hood. Consider using a respirator if engineering controls are inadequate (per SDS).
• Handling: Avoid heat, sparks, and open flames during operations; although not highly volatile, hot charging can produce irritating fumes. Prevent environmental release.
• Incompatibilities: Strong bases at elevated temperature can induce benzyne-type chemistry; strong nucleophiles under forcing conditions may displace bromide. Avoid strong oxidizers and finely divided reactive metals.
• First aid (overview; defer to SDS): • Inhalation: Move to fresh air; seek medical attention if symptoms persist.
  • Skin contact: Remove contaminated clothing; wash with soap and water.
  • Eye contact: Rinse cautiously with water for several minutes; remove contacts if easy; get medical attention.
  • Ingestion: Rinse mouth; do not induce vomiting; seek medical advice.
• Fire-fighting: Use dry chemical, CO2, or foam. Combustion/thermal decomposition may release HBr, HF, and other corrosive halogenated fumes—self-contained breathing apparatus recommended.
• Spill response: Absorb with inert material; collect for disposal as halogenated organic waste. Prevent entry into waterways.

Always consult the product’s SDS for definitive hazard and response information.

Solvent Selection

This product is a halogenated aromatic building block, not typically used as a bulk solvent. Selection here refers to solvents for its handling, purification, and reactions.

• Polarity/miscibility (qualitative, literature): Poorly soluble in water; good solubility in common organic solvents such as toluene, xylene, dichloromethane (DCM), chloroform, ethyl acetate, acetone, THF, dioxane, DMF, DMAc, and NMP.
• Typical use scenarios: • Cross-coupling (Suzuki, Buchwald–Hartwig): toluene, dioxane, THF, or IPA/H2O mixtures with base (K2CO3, K3PO4, Cs2CO3).
  • Sonogashira/Heck: DMF, DMAc, NMP, or acetonitrile; triethylamine or DIPEA for Sonogashira.
  • Lithiation/metal–halogen exchange (if attempted): anhydrous etheral solvents (THF, MTBE) at low temperature; CF3 deactivation requires careful conditions.
• Purification: Flash chromatography with hexanes/EtOAc or hexanes/CH2Cl2 gradients; high halogen content often gives strong UV response at 254 nm.

Quick comparison (literature-guided):

• Toluene vs dioxane: toluene favors higher temperatures and phase-transfer setups; dioxane/THF improve solubility of inorganic bases.
• DMF/DMAc/NMP: enhance rates for couplings but pose higher EHS burdens; consider 2-MeTHF, CyMe4-BuOH (TAME derivatives), or propylene carbonate for greener alternatives if compatible.

Practical tips:

• Dry, degas solvents when using in Pd/Ni catalysis to minimize protodehalogenation.
• Check substrate solubility at reaction temperature; concentrate solutions can gel upon cooling due to high halogen content—maintain gentle heat for transfers.

Storage and Reconstitution

• Storage conditions: Room temperature (item-specific, per Product Data). Store tightly closed in a dry, well-ventilated place. Protect from moisture and prolonged light/heat exposure.
• Shipped in: Normal (item-specific, per Product Data).
• Reconstitution: Not applicable—use as supplied (neat) or dissolve in a suitable anhydrous organic solvent (e.g., toluene, THF, DCM, DMF) immediately prior to use.
• Stability considerations (general): Aryl bromides are typically stable under ambient conditions when protected from moisture and strong light. For prolonged storage, inert gas blanket (N2/Ar) is prudent. Avoid contact with strong bases or nucleophiles unless in controlled reaction settings.
• Freeze–thaw: Not relevant; do not store in a way that allows repeated condensation of atmospheric moisture inside the container. If crystallization occurs upon cooling, gently warm to re-dissolve before use (if the material is a high-boiling liquid).
• Packaging: Prefer amber glass with PTFE-lined cap to minimize permeation and halogen–polymer interactions.

Always consult the product label and CoA/SDS for lot-specific handling and stability information.

Structure and Identity

Brief overview: 2,5-Dibromobenzotrifluoride is a brominated, trifluoromethyl-substituted aromatic building block useful for cross-coupling and other Pd-catalyzed transformations.

• SKU: D123763
• Product name: 2,5-Dibromobenzotrifluoride
• CAS: 7657-09-2 (item-specific)
• CID (PubChem): 82108 (item-specific)
• InChIKey: 390249 (item-specific)
• SMILES: Not specified for this item; refer to CoA/Spec Sheet.
  • Representative SMILES (literature): Brc1ccc(Br)c(C(F)(F)F)c1
• Molecular formula: Not specified for this item; refer to CoA/Spec Sheet.
  • Typical formula (literature): C7H3Br2F3
• Molecular weight: Not specified for this item; refer to CoA/Spec Sheet.
  • Typical MW (literature): ~303.90 g/mol for C7H3Br2F3

Structural features (general description):

• Aromatic ring bearing two aryl–Br bonds positioned 1,4 to each other relative to the para axis defined by the CF3 substituent; specifically bromides at the 2- and 5-positions with a CF3 at the 1-position.
• Functional groups: two aryl bromides (good cross-coupling leaving groups); one strongly electron-withdrawing trifluoromethyl group (–I, –M weak), which deactivates the ring toward electrophilic substitution and influences regioselectivity in metalation.
• No stereocenters; achiral, planar aromatic system.
• Electronic profile: CF3 reduces aryl π-basicity, stabilizes anionic intermediates para/ortho to CF3 poorly; bromides enable oxidative addition under Pd/Ni catalysis.
• 2D description in words: a benzene ring with CF3 at C1, Br substituents at C2 and C5; remaining ring positions are hydrogen.

Synthetic Utility

Key functional groups and reactivity (literature/general):

• Two aryl bromides: versatile electrophiles for Pd/Ni-catalyzed cross-couplings (Suzuki, Buchwald–Hartwig, Sonogashira, Negishi, Kumada). The 2,5-arrangement facilitates creation of meta/para arrays relative to CF3.
• CF3 substituent: strongly deactivating and meta-directing in electrophilic substitution; increases lipophilicity and can influence conformational preferences and π-stacking in targets.

Retrosynthetic value:

• Enables convergent assembly of diaryl or aryl–alkynyl scaffolds from a single core. Orthogonal or sequential coupling allows library synthesis by varying the partner at C2 vs C5 with ligand-controlled selectivity.
• Post-coupling diversification:
  • Hydrogenation of alkynes (from Sonogashira) to alkanes/alkenes.
  • Directed C–H activation on appended motifs.
  • Nucleophilic aromatic substitution on introduced electron-poor rings.

Named transformations (typical literature conditions):

• Suzuki–Miyaura: Pd(PPh3)4 or Pd-precatalysts; K3PO4/Cs2CO3; toluene/dioxane/H2O; 60–110 °C.
• Buchwald–Hartwig amination: Pd2(dba)3 + BINAP/DavePhos/XPhos; NaOtBu or Cs2CO3; toluene/dioxane; 80–110 °C.
• Sonogashira: Pd(PPh3)2Cl2/CuI; Et3N or i-Pr2NEt; THF/DMF; 25–80 °C.
• Negishi/Kumada: Pd or Ni catalysts with organozinc or Grignard partners at 0–60 °C.

Purification/analysis tips:

• Monitor reactions by GC or LC–MS; the heavy-atom isotopic envelope (Br2) simplifies identification. 19F NMR provides a convenient handle for conversion/impurity tracking.

Target Specificity

Not applicable. This product is a small-molecule building block and does not target biological epitopes or possess antibody/assay specificity.

• Antigen/epitope: Not applicable.
• Species reactivity/clone/isotype: Not applicable.